The recombinant human fusion protein L19TNFα was created with the intention to overcome the systemic toxicity of TNFα by directly targeting it to tumor tissues. Tumor-targeted L19TNFα would result in high and sustained intralesional bioactive TNFα concentrations.

Determination of the Maximum Tolerated Dose (MTD) and Recommended Dose (RD) of L19TNFα.

Phase II: Investigation of the anti-cancer activity of L19TNFα as measured by Objective Response Rate (ORR) [ Time Frame: within day 42 ] [ Designated as safety issue: No ]

Investigation of the anti-cancer activity of L19TNFα as monotherapy as measured by the Objective Response Rate (ORR) at the end of cycle 2 in subjects with relapsed or refractory locally advanced or metastatic colorectal cancer not amenable to standard systemic therapy.

Investigation of early signs of anti-tumor activity of L19TNFα [ Time Frame: 14 months ] [ Designated as safety issue: No ]

Investigation of early signs of anti-tumor activity of L19TNFα as measured by Objective Response Rate (ORR) at the end of cycle 2, median Progression-Free Survival (PFS) and median Overall Survival (OS).

Schedule: Infusions of L19TNFα on days 1, 3 and 5 of each 21-day cycle. Patients may remain on treatment for a maximum of six 21-day cycles.

Detailed Description:

The primary purpose of this Phase I/II study is to define a safe and potentially active treatment regimen of L19TNFα as a monotherapy and to evaluate the antitumor activity of this regimen in relapsed metastatic colorectal cancer subjects, for whom standard treatment options are exhausted. L19TNFα is an investigational drug that specifically and effectively binds to ED-B, which is abundantly expressed in cancer tissue. Accordingly, treatment should result in a high and long-lasting intratumoral accumulation of biologically active rh-TNFα. Although combined therapies of TNFα with cytotoxic drugs (e.g. melphalan) seem to be strikingly more active against sarcoma and melanoma than with TNFα alone - at least for the ILP setting it seems possible that the repeated intratumoral delivery of TNFα via L19TNFα might produce additional biologic effects, such as the induction of an immunologic antitumor response or the sustained inhibition of tumor-associated angiogenesis (Lejeune, 2006), that potentially could benefit advanced cancer subjects.

Eligibility

Ages Eligible for Study:

18 Years and older (Adult, Senior)

Genders Eligible for Study:

Both

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria:

Phase I: histologically or cytologically confirmed relapsed or refractory locally advanced or metastatic solid tumor of any origin, not amenable to standard therapy.

Subjects must have at least one unidimensionally measurable lesion by computed tomography as defined by RECIST criteria (see Section 8) or tumour markers parameters of disease such as PSA and CA125 for Prostate cancer and Ovarian cancer, respectively. This lesion must not have been irradiated during previous treatments.

Testing negative for acute or chronic infection with hepatitis B or C virus, or human immunodeficiency virus 1 or 2.

Negative pregnancy test for females of childbearing potential at the screening visit.

Commitment from subject to practice medically appropriate/acceptable method of birth control (e.g., hormonal, condoms or other adequate barrier controls, intrauterine contraceptive device, or sterilization) beginning at the screening visit and continuing until 3 months following the last treatment with study drug.

Able to provide written Informed Consent.

Exclusion Criteria:

Breastfeeding women.

Presence of active infections (e.g. requiring antimicrobial therapy) or other severe concurrent disease, which, in the opinion of the Investigator, would place the subject at undue risk or interfere with the study.

Previous in vivo exposure to monoclonal antibodies for biological therapy in the 6 weeks before administration of study treatment.

Growth factors or immunomodulatory agents within 7 days prior to the administration of the study treatment.

Subject requires or is taking corticosteroids or other immunosuppressant drugs on a long-term basis. Limited use of corticosteroids to treat or prevent acute hypersensitivity reactions is not considered an exclusion criterion.

Concurrent therapy with warfarin at doses greater than 1 mg/day or equivalent doses of other coumarin derivatives.

Participation in another interventional clinical trial during participation in this trial.

Expectation that the subject will not be able to complete at least 6 weeks of therapy.

Any conditions that in the opinion of the Investigator could hamper compliance with the study protocol.

Contacts and Locations

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To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01253837